Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Reviewing the evidence for autologous SCT in newly diagnosed type 1 diabetes (#319)

Benjamin Kwan 1 2
  1. Department of Endocrinology, Concord Repatriation General Hospital, Concord, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia

Context and Aims: Stem cells are characterised by their plasticity and pluripotency. Their regenerative and immunomodulatory properties offer the potential for β-cell preservation and regeneration in type 1 diabetes (T1D). Autologous HSC transplantation (auHSCT) under non-myeloablative conditioning can serve as an immunological ‘reset’ and has been studied in other autoimmune conditions. Autoreactive T-cell populations are abolished by conditioning chemotherapy, then replaced by a regenerated immune system from haematopoietic progenitors.

Methods: A comprehensive review of published literature on auHSCT in T1D was undertaken.

Findings: A Brazilian study1,2 of 23 patients with newly diagnosed T1D (diagnosis < 6 weeks, GAD Ab positive, DKA excluded) found that auHSCT with non-myeloablative conditioning led to insulin independence in 20/23 patients. Twelve patients (52%) were continuously insulin independent over a mean 31 months, with significant improvements in HbA1c and AUC C-peptide up to 36 months. Similar findings were seen in a Polish study of eight patients.3 A Chinese study found lower rates of insulin independence (23%) in patients with established T1D (>12 months).4 Adverse effects from treatment included nausea, alopecia, fever, and oligospermia. Less toxic conditioning regimes (cyclophosphamide, fludarabine) have been trialled successfully in the outpatient setting. In one study of 16 patients, response was seen in 81% of patients (reduced insulin requirements and GAD Ab titre), while long term insulin independence was seen in 44% after follow-up of 21-56 months.5

Improvements in β-cell function are thought to be independent of a prolonged ‘honeymoon’, given its duration and sustained C-peptide responses. A proposed mechanism is upregulation of regulatory CD4+ CD25+ Foxp3+ T cells and apoptotic gene expression suggesting a shift toward immune tolerance.6,7

Implications: Early clinical trials suggest auSCT may lead to long-term insulin independence through immune-mediated beta-cell preservation in T1D. Further clinical research is necessary to establish its efficacy and safety.

  1. Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F et al. (2007). Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA, 297(14):1568-76
  2. Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM et al. (2009). C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA, 301(15):1573-9
  3. Snarski E, Milczarczyk A, Torosian T, Paluszewska M, Urbanowska E, Król M et al. (2011). Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I. Bone Marrow Transplant, 46(4):562-6
  4. Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W et al. (2012). Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes. J Clin Endocrinol Metab, 97(5):1729-36
  5. Cantú-Rodríguez OG, Lavalle-González F, Herrera-Rojas MÁ, Jaime-Pérez JC, Hawing-Zárate JÁ, Gutiérrez-Aguirre CH et al. (2016). Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant. J Clin Endocrinol Metab, 101(5):2141-8
  6. Voltarelli JC, Couri CEB, Oliveira MC, Moraes DA, Stracieri ABPL, Pieroni F et al. (2011). Stem cell therapy for diabetes mellitus. Kidney Int Suppl, 1(3):94–98
  7. de Oliveira GL, Malmegrim KC, Ferreira AF, Tognon R, Kashima S, Couri CE et al. (2012). Up-regulation of fas and fasL pro-apoptotic genes expression in type 1 diabetes patients after autologous haematopoietic stem cell transplantation. Clin Exp Immunol, 168(3):291-302